Large-Scale Discovery of Functional Genetic Variation in Rhesus Macaques

大规模发现恒河猴功能遗传变异

基本信息

批准号：
8325549
负责人：
JEFFREY A. ROGERS
金额：
$ 54.09万
依托单位：
BAYLOR COLLEGE OF MEDICINE
依托单位国家：
美国
项目类别：
财政年份：
2011
资助国家：
美国
起止时间：
2011-09-01 至 2015-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8325549
关键词：
Acquired Immunodeficiency Syndrome Alcoholism Animal Model Animals Anxiety Disorders Archives Biological Factors Biomedical Research Cataloging Catalogs Chinese People Communicable Diseases Communities DNA DNA Sequence Data Databases Development Diabetes Mellitus Disease Disease Progression Disease susceptibility Drug Addiction Exhibits Exons Funding Gene Expression Genes Genetic Genetic Polymorphism Genetic Transcription Genetic Variation Genome Genomics Goals HIV HIV Infections HIV vaccine Health Human Individual Investigation Knowledge Leukocytes Lymphocyte Macaca Macaca mulatta Mental Depression Metabolic Diseases Methods Modeling Molecular Genetics National Human Genome Research Institute Neurobiology Neurosciences Obesity Osteoporosis Pan Genus Pathogenesis Primates Principal Investigator RNA Sequences Reading Reproductive Biology Reproductive Endocrinology Research Research Personnel Resources Risk SIV Subfamily lentivirinae Tissues United States National Institutes of Health Variant base developmental psychobiology exome genome sequencing innovation interest nonhuman primate novel novel vaccines response stem cell biology

项目摘要

DESCRIPTION (provided by applicant): Rhesus macaques (Macaca mulatta) are the most widely used nonhuman primate in biomedical research. Rhesus are critically important in efforts to understand the pathogenesis of HIV-AIDS, to develop novel treatments and new vaccines against HIV infection. In addition, rhesus macaques are commonly used in studies of basic neurobiology, metabolic diseases such as diabetes and osteoporosis, and reproductive biology. Rhesus monkeys are important in analyses of stem cell biology. This species is also frequently used as an animal model in studies related to alcoholism, drug addiction, anxiety disorders and depression. This proposed project will dramatically increase the value and significance of this primate species for all types of biomedical research by generating a substantial amount of new information about functional genetic variation among rhesus macaques. It is now well established that genetic differences among people influence their risk of developing common diseases such as those listed above, including infectious diseases. Genetic variation can also influence the progression of disease and the responses of different people to a specific treatment. We will facilitate research on the genetic basis of disease susceptibility and response to treatment by identifying large numbers of new DNA sequence variants in functional genes within the rhesus genome. To accomplish this, we will sequence the exome (all functional gene exons) from 96 unrelated rhesus macaques, both Indian-origin and Chinese-origin animals. We will also produce whole genome sequences for 8 of those 96 animals. The exome and whole genome data will be used to identify new DNA sequence variation present in this species. We will also sequence RNA from the lymphocytes of all 96 animals to begin assessment of individual variation in gene expression within that tissue, and to correlate differential RNA expression with DNA sequence variation in the relevant genes. All the data generated will be made publically available through appropriate NCBl databases (e.g. Short Read Archive, dbVAR and dbSNP) and by creating our own public searchable on-line database of rhesus genetic variation.

描述（由申请人提供）：恒河猴（Macaca mulatta）是生物医学研究中使用最广泛的非人类灵长类动物。恒河猴对于了解艾滋病毒/艾滋病的发病机制、开发针对艾滋病毒感染的新疗法和新疫苗至关重要。此外，恒河猴还常用于基础神经生物学、糖尿病和骨质疏松症等代谢疾病以及生殖生物学的研究。恒河猴在干细胞生物学分析中很重要。该物种也经常被用作酒精中毒、吸毒成瘾、焦虑症和抑郁症相关研究的动物模型。该拟议项目将通过产生大量有关恒河猴功能性遗传变异的新信息，极大地提高该灵长类物种对所有类型生物医学研究的价值和意义。现在已经明确，人与人之间的遗传差异会影响他们患上上述常见疾病（包括传染病）的风险。遗传变异还会影响疾病的进展以及不同人对特定治疗的反应。我们将通过鉴定恒河猴基因组内功能基因中的大量新 DNA 序列变异，促进对疾病易感性和治疗反应的遗传基础的研究。为了实现这一目标，我们将对 96 只无关的恒河猴（印度和中国的动物）的外显子（所有功能基因外显子）进行测序。我们还将生产这 96 只动物中 8 只的全基因组序列。外显子组和全基因组数据将用于识别该物种中存在的新 DNA 序列变异。我们还将对所有 96 只动物的淋巴细胞进行 RNA 测序，以开始评估该组织内基因表达的个体差异，并将差异性 RNA 表达与相关基因中的 DNA 序列变异联系起来。生成的所有数据将通过适当的 NCBl 数据库（例如 Short Read Archive、dbVAR 和 dbSNP）以及创建我们自己的恒河猴遗传变异公共可搜索在线数据库公开提供。